Objective: Fine needle aspiration (FNA) is a reliable method in the initial assessment of thyroid nodules. The purpose of this study was to evaluate the causes for discordance between the interpretation on FNA and the pathologic findings in the resected thyroid. Methods: A computer search of all thyroidectomy specimens with previous FNA from January 1998 to December 2001 was obtained from the files of the Lauren V. Ackerman laboratory of surgical pathology, Barnes-Jewish Hospital. Excluded from the study were those FNAs performed for suspected and confirmed metastatic disease to the thyroid as well as those cases unavailable for review. A total of 45 FNA cases were identified with cytologic and histologic discrepancies. Results: Of the 1253 individual thyroid FNA performed during the study period, 255 patients (20%) subsequently had an open surgical procedure on the thyroid. Of those who underwent surgery, 196 cases (77%) were concordant, whereas 45 patients (18%) were discordant, and 14 cases were excluded due to unavailability of slides for review (for example, returned consult slides). The causes of the 45 discordant cases were: 20 cases (44%) were unsatisfactory for diagnosis, 14 cases (31%) were due to interpretation error (false positive), and 11 cases (24%) were due to sampling error (false negative). Conclusions: The most common causes of our discrepant cases are those whose FNA diagnosis was interpreted as "unsatisfactory for diagnosis," in 20 (7.8%) of 255 surgical cases. The false negative rate due to sampling error in 11 (4%) of 255 cases was mainly due to the presence of microscopic papillary thyroid carcinoma (PTC); the false positive rate was due to interpretation error in 14 (6%) of 255 cases, and those were explained by the occurrence of overlapping cytologic features among adenomatous nodules, follicular neoplasms, the follicular variant of PTC, and Hashimoto's thyroiditis.